BMC128: A rationally designed live bacterial consortium for the potentiation of immune checkpoint therapy in solid tumors.

TPS2685 Background: Immune-Checkpoint inhibitors (ICI) have transformed the treatment of solid tumors, specifically in cutaneous melanoma, clear cell renal cell carcinoma (ccRCC) and non-small cell lung cancer (NSCLC). Despite these advances, a significant proportion of patients do not respond to ICI and only a fraction of responding patients will experience durable responses. Recent reports have found that patients showing poor response to ICI are characterized by a reduced gut microbiome diversity, suggesting that the gut microbiome might affect immune activation by ICI. BMC128 is a live bacterial consortium of 4 bacterial strains predicted to induce anti-tumor immune function when given in conjunction with ICI. These strains were identified by analyzing data obtained from NSCLC and ccRCC patients presenting varied responses to ICI, using a proprietary computational discovery platform enabling high-resolution functional microbiome analysis. In pre-clinical studies, treatment with BMC128 potentiated the efficacy of ICI in breast cancer and melanoma mouse models, reducing tumor volume, increasing the number of responders, and demonstrating an increase in infiltrating immunocytes: CD4, CD8 and NK cells. Methods: In this phase I, first-in-human trial, patients with ccRCC, cutaneous melanoma and NSCLC-adenocarcinoma (EGFR/ALK wild-type), who previously progressed on PD1/PDL-1 inhibitors will be treated with BMC128 8*108 CFU BID in combination with Nivolumab at a fixed-dose of 480mg q4weeks in a 3+3 design, followed by a 9 patient expansion phase. No dose escalation is planned. The primary objective is to investigate the safety and tolerability of BMC128 in combination with Nivolumab. Enrollment is intended to start in Feb, 2022. Clinical trial information: 202122207. [Table: see text]